Yale OAIC activities will focus on multifactorial geriatric health conditions-health conditions common among older persons that result from combinations of multiple factors, that may be prevented by multifactorial interventions, and that trigger multiple possible outcomes. Building on the foundation laid over previous periods of OAIC support, we will focus on identifying solutions to barriers impeding a more complete understanding of the etiology, prevention, treatment, and outcomes of multifactorial geriatric conditions. We propose a portfolio that includes: 1) investigations of traditional disease entities such as recurrent MI and pneumonia from the novel perspective of the geriatric syndrome model; 2) methodologic projects that take our epidemiologic and intervention studies to the next level of complexity by developing longitudinal methods for analyzing the effect of precipitating events on outcomes and for handling the common occurrence of bi-directionality (feed back loops) between risk factor or treatment and outcome and methods for determining the mechanisms of action of multifactorial intervention strategies; 3)novel applications of existing technologies, such as Geographic Information Systems, to evaluate the penetration, and effectiveness of real world implementation of multifactorial interventions; 4) the categorization, analysis, and dissemination of new and existing measures of multiple domains for use by investigators throughout all OAICs; 5) exploratory projects such as the development of a strategy for eliciting older persons' treatment goals when faced with multifactorial geriatric health conditions; and 6) capitalizing on unanticipated research opportunities and encouraging potential translational research as exemplified by a proposed pilot which examines alterations in oxidative stress responsiveness with human aging. This last project is particularly exciting because the paradigms guiding this work at the cellular level parallel those guiding Yale OAIC work at the human level, thus offering the promise of breakthrough discoveries concerning the etiology, prevention and treatment, of multifactorial geriatric health conditions. To support these, and other, projects the Yale OAIC will include the following Cores: 1) leadership/ administrative; 2) research career development which will offer early career, transitional career, and affiliated faculty, Development awards; 3) Pilot/exploratory studies; 4) Field; 5) Data Management/lnformatics; 6) Biostatistics.